The present invention is directed to colored enhanced concentrated esmolol formulations including a color additive. More specifically, the invention is directed to a concentrated esmolol formulation having a non-toxic color additive preferably approved for parenteral administration, preferably approved for I.V. administration. The invention is directed to a concentrated esmolol formulation having a color sufficient to be easily distinguishable from a dilution of the concentrate of at least a ratio of about one part concentrate to four parts diluent (1:4).
Administration of the proper dosage of a medication is one area where errors can arise. Most medications are safe and effective at the proper dosage but can have adverse consequences at high dosages. In some cases, dosing errors can have life threatening consequences.
Dosing errors can unfortunately occur with respect to liquid medications that are provided in various strengths. This is especially true where the concentrated form of the medication is visually indistinguishable from a diluted form such as with substantially clear and colorless liquids. Liquid medications can come as ready-to-use formulations and in concentrated formulations, which require dilution prior to administration. Usually the only means of differentiating between concentrated and diluted formulations is by the labeling of the container housing the medication. As an added precaution, the container itself or the closure may be given distinct attributes such as coloring. However, errors still occur because often times the medication is transferred to a secondary container such as a syringe.
In order to assist health care practitioners to identify potentially hazardous concentrated potassium chloride formulations, there have been attempts to include a color additive. One known colored, potassium chloride concentrate uses methylene blue to assist practitioners in identifying the concentrate over the diluted form. Unfortunately, due to the shortcomings of this colored concentrated potassium chloride formulation, coloring concentrated medical formulations have not been adopted with all medications in which the concentrated form can be potentially hazardous if administered directly and where the concentrated form of the medication is substantially indistinguishable from the diluted form.
There are many commonly used safe and effective liquid medications that in concentrated form could be potentially hazardous and in which the concentrate liquid is indistinguishable from a diluted form of the liquid. One widely used liquid medication that can be provided both in concentrated form and a diluted ready-to-use form is methyl-3-[4-(2-hydroxy-3-isopropylamino) propoxy]phenylpropionate hydrochloride (esmolol hydrochloride).
Esmolol (and its pharmaceutically acceptable salts, e.g., hydrochloride salt) and related compounds have β-adrenergic blocking activity. β-blockers are therapeutically effective agents for the treatment and prophylaxis of cardiac disorders when administered in the appropriate dosage. However, high doses can cause dangerously low cardiac output. Esmolol, which is a short-acting β-blocker, is often times used in acute care settings to control the heart rate of a patient. Ready-to-use isotonic and concentrated formulations of esmolol hydrochloride and related compounds are disclosed in U.S. Pat. Nos. 5,017,609, 6,310,094, and 6,528,540, incorporated herein by reference. Methods for making esmolol and related compounds and methods for treatment or prophylaxis of cardiac disorders using such compounds are disclosed in U.S. Pat. Nos. 4,387,103 and 4,593,119, incorporated herein by reference.
Since esmolol formulations are substantially clear and colorless, the concentrated formulation is visually indistinguishable from a diluted formulation. Since esmolol hydrochloride can be provided as either a concentrate or in ready-to-use strength, it is desirable to have some means of identifying the concentrate once it has been removed from its primary container.
It would be desirable to provide a concentrated esmolol formulation that is readily distinguishable from a dilution of the colored concentrate.